Schizophrenia is associated with an unusually high rate of cigarette smoking. Smokers with schizophrenia have low quit rates, even when they are motivated to quit and enroll in highly-supportive treatments. The overall aim of this research program is to learn how biological and environmental factors control smoking in smokers with schizophrenia and to use this knowledge to design more effective smoking treatments for these patients. The specific objectives of this R21 Exploratory/ Developmental project are to test two hypotheses concerning the low cessation rates in smokers with schizophrenia: (1) that these smokers experience more severe and sustained levels of negative affect during abstinence than equally-heavy smokers without psychiatric illness, and (2) that smokers with schizophrenia experience stronger reinforcing effects of smoking and specifically of nicotine during a smoking lapse than smokers without psychiatric illness. These hypotheses have solid theoretical and preclinical support, but have not been tested in humans. In this exploratory/ developmental study, we will use high-value contingent monetary reinforcement to engender 3 days of continuous abstinence in smokers with schizophrenia and equally-heavy smokers without psychiatric illness. During the abstinence period, negative affect and smoking urge will be measured twice-daily. Laboratory assessments of nicotine preference and hedonic response to smoking will be conducted at baseline and after the abstinence period. After the second nicotine preference task, participants will receive a small-value reinforcer if they continue to abstain for another day. We will then compare latency to the second lapse in these groups and examine predictors of the second lapse. Smokers with schizophrenia are expected to have stronger levels of negative affect and craving during abstinence and stronger reinforcing effects of nicotine and smoking during the programmed lapse. These factors are expected to predict time to second lapse in both groups. This project will expand existing knowledge concerning factors that affect smoking in people with schizophrenia, which is necessary for the development of effective treatments for these smokers. PUBLIC HEALTH RELEVANCE: There is an unusually high rate of cigarette smoking among people with schizophrenia and correspondingly high rates of smoking-related morbidity and mortality in these patients. The aim of this project is to compare, in smokers with schizophrenia and heavy smokers without psychiatric illness, negative affect and craving during a practice quit attempt and positive reinforcing effects of a smoking lapse. This project will expand existing knowledge concerning factors that affect smoking in people with schizophrenia, which is necessary for the development of effective treatments for these smokers.